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WO1996031195A1 - Emballage contenant une formulation de solution aqueuse de chlorhydrate de procaterol et formulation de solution aqueuse de chlorhydrate de procaterol - Google Patents

Emballage contenant une formulation de solution aqueuse de chlorhydrate de procaterol et formulation de solution aqueuse de chlorhydrate de procaterol Download PDF

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Publication number
WO1996031195A1
WO1996031195A1 PCT/JP1996/000772 JP9600772W WO9631195A1 WO 1996031195 A1 WO1996031195 A1 WO 1996031195A1 JP 9600772 W JP9600772 W JP 9600772W WO 9631195 A1 WO9631195 A1 WO 9631195A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
aqueous solution
procaterol hydrochloride
water
molecular
Prior art date
Application number
PCT/JP1996/000772
Other languages
English (en)
Inventor
Yuzo Kimura
Shinichi Ishikawa
Masafumi Toda
Takakuni Matsuda
Original Assignee
Otsuka Pharmaceutical Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Otsuka Pharmaceutical Co., Ltd. filed Critical Otsuka Pharmaceutical Co., Ltd.
Priority to EP96906940A priority Critical patent/EP0820274A1/fr
Priority to MX9707695A priority patent/MX9707695A/es
Priority to AU50152/96A priority patent/AU5015296A/en
Publication of WO1996031195A1 publication Critical patent/WO1996031195A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4704—2-Quinolinones, e.g. carbostyril

Definitions

  • the present invention relates to a pharmaceutical composition comprising an aqueous solution of procaterol hydrochloride and a package which holds the pharmaceutical composition comprising an aqueous solution of procaterol hydrochloride.
  • Procaterol hydrochloride in a low concentration has drawbacks of being unstable in an aqueous solution and low in long-term storage stability.
  • the procaterol hydrochloride in a low concentration has a further disadvantage that it readily flows away by dint of our tear or snivel after administration.
  • An object of the present invention is to impart long-term storage stability to a pharmaceutical composition comprising an aqueous solution of procaterol hydrochloride (hereinafter referred to as "procaterol hydrochloride aqueous solution formulation") in a low concentration.
  • Another object of the invention is to provide a procaterol hydrochloride aqueous solution capable of producing a prolonged effect after its application to the eye or the like.
  • the present inventors conducted extensive research to impart long-term storage stability to a procaterol hydrochloride aqueous solution formulation in a low concentration and found that the procaterol hydrochloride in a low concentration is decomposed in the aqueous solution by the oxidation reaction of the procaterol hydrochloride in the solution and that the oxidation reaction is not allowed to proceed in the absence of oxygen.
  • the present invention has been completed based on these novel findings.
  • a package holding a pharmaceutical composition comprising an aqueous solution of procaterol hydrochloride such that the procaterol hydrochloride is kept from decomposing in the aqueous solution due to its oxidation reaction.
  • the decomposition of procaterol hydrochloride in an aqueous solution due to its oxidation can be prevented, for example, by maintaining the procaterol hydrochloride aqueous solution formulation under an oxygen-free atmosphere.
  • the oxygen-free atmosphere can be produced by replacing the air in a glass container with nitrogen gas and sealing the container.
  • Plastics containers most widely used for ophthalmic solutions have too high a gas permeability to retain the oxygen-free atmosphere even after replacement with nitrogen gas.
  • the procaterol hydrochloride aqueous solution formulation is filled in a plastics container, and the container is packaged in a gas barrier packaging material.
  • the present inventors' research found the following. When a plastics ophthalmic container full of an aqueous solution of procaterol hydrochloride is accommodated and sealed, together with an oxygen absorbent, in a bottle or a bag made of a gas-impermeable film, there is obtained a procaterol hydrochloride aqueous solution formulation which is excellent in the long-term storage stability.
  • a preferred embodiment of the package holding the procaterol hydrochloride aqueous solution formulation according to the invention is a package holding the procaterol hydrochloride aqueous solution formulation wherein the procaterol hydrochloride aqueous solution formulation is enclosed in a plastics container, and wherein the container is packaged, together with an oxygen absorbent, in a gas barrier packaging material .
  • Another preferred embodiment of the package holding the procaterol hydrochloride aqueous solution formulation according to the invention is a package holding the procaterol hydrochloride aqueous solution formulation wherein the procaterol hydrochloride aqueous solution formulation is enclosed in a plastics container; wherein the container is packaged in a gas barrier packaging material; and wherein a nitrogen gas and/or carbon dioxide gas is sealed in a space between the container and the gas barrier packaging material.
  • the present inventors further found that the effect of the procaterol hydrochloride solution formulation can be prolonged by incorporating into the formulation a water-soluble high-molecular-weight compound containing an anionic functional group and having a molecular weight of at least 10,000, preferably at least one water-soluble high-molecular-weight compound selected from the group consisting of acidic mucopolysaccharide and dextran sulfate containing a sulfuric acid group, and salts thereof.
  • procaterol hydrochloride aqueous solution formulation incorporating therein at least one high-molecular-weight compound containing an anionic functional group and having a molecular weight of at least 10,000.
  • plastics containers can be used as the container for accommodating the procaterol hydrochloride aqueous solution formulation according to the invention.
  • the materials useful for the plastics containers are not specifically limited and can be known plastics such as polyethylene, polypropylene and like polyolefins, copolymers thereof, polyvinyl chloride, ethylene-vinyl acetate copolymers, polyester, nylon, polycarbonate, polyethylene terephthalate, etc. A combination of at least two of these same or different polymers having a complex multilayered structure may also be used.
  • the procaterol hydrochloride aqueous solution formulations of the present invention include various formulations such as ophthalmic solutions, insufflation- type solutions, rhinal solutions, etc. Among them, ophthalmic solutions are preferred.
  • procaterol hydrochloride ophthalmic solutions are described below in detail.
  • the ophthalmic solution can be prepared in the conventional manner. Stated more specifically, procaterol hydrochloride as an active ingredient is mixed with a suitable carrier and the mixture is treated for sterilization. Suitable carriers include, for example, sterilized and purified water. When required, such ophthalmic solutions may contain any of various conventional additives such as solubilizing agents, buffers, antioxidants, stabilizers, antiseptics, isotonizing agents, pH adjusters, thickeners, etc.
  • useful solubilizing agents are sodium carboxymethyl cellulose, polyoxyethylene glycol ethers such as polyoxyethylene lauryl ether, polyoxyethylene oleyl ether, etc., polyethylene glycol higher fatty acid esters such as polyethylene glycol monolaurate, polyethylene glycol monooleate, etc., polyoxyethylene sorbitan monolaurate, polyoxyethylene fatty acid ester, etc.
  • useful buffers are sodium phosphate, sodium hydrogenphosphate, potassium hydrogenphosphate, boric acid, sodium borate, citric acid, sodium citrate, tartaric acid, sodium tartrate, acetic acid, sodium acetate, ⁇ -amino caproic acid, sodium gluta ate, etc.
  • Useful antioxidants include, for example, sodium sulfite, sodium pyrosulfite, sodium bisulfite, sodium thiosulfite, ascorbic acid, etc.
  • Useful stabilizers include, for example, ethylenediaminetetraacetic acid (EDTA), hydroxyquinolin sulfate, etc.
  • Useful antiseptics are, for example, chlorobutanol, benzalkonium chloride, benzethonium chloride, mercuryphenyl salt, thi erosal, phenethyl alcohol, methylparaben, ethylparaben, propylparaben, butylparaben, etc.
  • Useful isotonizing agents are sodium chloride, glucose, D-mannitol, glycerin, etc.
  • Useful pH adjusters are sodium hydroxide, hydrochloric acid, etc.
  • Useful thickeners are methyl cellulose, hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose and like cellulose derivatives, hydroxyethyl starch, methyl starch and like starch derivatives, polyvinyl alcohol, polyvinyl pyrrolidone, etc.
  • insufflation-type solutions and rhinal solutions are formulated in the same manner as said procaterol hydrochloride ophthalmic solutions.
  • an isotonizing agent need not be incorporated.
  • a wide variety of conventional compounds are usable as at least one water-soluble high-molecular-weight compound containing an anionic functional group which is used in the invention to prolong the effect of the procaterol hydrochloride.
  • Such compounds include, for example, hyaluronic acid, chondroitin sulfate, carrageenan, chitin sulfate, ' chitosan sulfate, pullulan sulfate, alginic acid, carboxymethyl cellulose, carboxy- ethylcurdlan, carboxymethyldextran, carboxymethylpullu- lan, carboxymethylchitin, carboxymethylchitosan and like high-molecular-weight polysaccharides containing an anionic functional group and salts thereof, polystyrene- sulfonic acid, polyvinyl sulfate, polyacrylic acid, carboxyvinyl polymers, polymethacrylic acid and like synthetic high-molecular-weight compounds containing an ani
  • suitable compounds are those having a sulfuric acid group such as acidic mucopolysaccharide, dextran sulfate, polystyrenesulfonic acid and salts thereof. More specific examples are chondroitin sulfate, heparin, heparan sulfate, keratan sulfate, dextran sulfate, polystyrenesulfonic acid and salts thereof (e.g., sodium salt, potassium salt or calcium salt), etc.
  • a sulfuric acid group such as acidic mucopolysaccharide, dextran sulfate, polystyrenesulfonic acid and salts thereof. More specific examples are chondroitin sulfate, heparin, heparan sulfate, keratan sulfate, dextran sulfate, polystyrenesulfonic acid and salts thereof (e.g., sodium salt, potassium salt or calcium salt), etc.
  • chondroitin sulfate preferred are chondroitin sulfate, dextran sulfate, polystyrenesulfonic acid and salts thereof, and more preferred are sodium chondroitin sulfate, sodium dextran sulfate and sodium polystyrene sulfonate. Of them, most preferred is sodium chondroitin sulfate.
  • water-soluble high-molecular-weight compound having a molecular weight of at least 10,000, usually about 10,000 to about 3 millions. It is recommendable to use, in some cases, such compounds about 10,000 to about 100,000 in molecular weight and in other cases, those about 100,000 to about 1 million in molecular weight.
  • the amount of such water-soluble high-molecular- weight compound to be used is at least 10 mg/ml, preferably 10 to 150 mg/ml, more preferably 15 to 100 mg/ml, most preferably 20 to 50 mg/ml, based on the amount of the procaterol hydrochloride aqueous solution formulation.
  • the amount of the procaterol hydrochloride to be incorporated in the formulation is not critical but usually 0.1 to 10,000 ⁇ g/ml, preferably 1 to 1,000 ⁇ g/ml, more preferably 5 to 500 ⁇ g/ml. For use as an ophthalmic solution, the amount is 10 to 300 ⁇ g/ml.
  • Oxygen absorbents useful in the invention include those heretofore known and comprising, e.g., iron hydroxide, iron oxide, iron carbide or like iron compounds as an active ingredient.
  • Typical commercial products are, for example, those available under the tradenames
  • the form of the oxygen absorbent is not specifically limited insofar as the absorbent can be placed in the space between the plastics container holding the procaterol hydrochloride aqueous solution formulation and the gas barrier packaging material as its external cover.
  • the oxygen absorbent is in a powder form, preferably the required quantity of the powder is placed into a small-size air-permeable bag or the like, and the bag is laid in said space.
  • gas barrier packaging material which encloses therewith the plastics container holding the procaterol hydrochloride aqueous solution formulation.
  • these materials include glass containers, films or sheets and bottles made of various materials widely used, etc.
  • gas barrier materials containing at least one species selected from olefin resins such as polypropylene, high- density polyethylene or like polyethylenes, etc., polyethylene terephthalate, ethylene-vinyl alcohol copolymer resins, polyvinylidene chloride, polyacrylonitrile, polyvinyl alcohol, polycarbonate, polyamide resins such as nylon, etc., cellulose acetate, polyester, aluminum foil, glass and so on.
  • Gas barrier materials for use herein include laminated films of the above-exemplified materials, for example, laminated films of nylon, ethylene-vinyl alcohol copolymer resin and polyethylene, etc.
  • Gas barrier materials useful herein may be a laminate of aluminum foil and plastics such as polyethylene, a plastics film combined by vapor deposition with aluminum or silicic acid, etc.
  • Preferred gas barrier materials have an oxygen permeability of not higher than 1.0 ml/m 2 'hr»atm at 25°C and 75% RH.
  • the plastics container holding the procaterol hydrochloride aqueous solution formulation and the oxygen absorbent can be packaged (enclosed) in these packaging materials by conventional methods.
  • the package holding the procaterol hydrochloride aqueous solution formulation according to the present invention may be one produced without using an oxygen absorbent and by degassing the space between the plastics container and the gas barrier packaging material and sealing a nitrogen gas and/or carbon dioxide gas into said space.
  • the space can be degassed in the conventional manner using, e.g. a vacuum packaging machine.
  • the procaterol hydrochloride aqueous solution formulation of the present invention can be used for the purposes which cover all known applications of procaterol hydrochloride.
  • the formulation of the invention is suitable for use as a bronchodilator, peripheral vasodilators, antihypertensive, antiglaucoma, antiallergics, ophthalmic solutions for preventing and healing the inflammation and/or wound in eyes, etc.
  • the package holding the procaterol hydrochloride aqueous solution formulation according to the invention enhances the long-term storage stability of the formulation. Further the procaterol hydrochloride aqueous solution formulation containing the foregoing specific water-soluble high-molecular-weight compound can produce markedly prolonged effects. Examples
  • Methylparaben 0.5 mg pH adjuster q.s.
  • Hydrochloric acid (pH adjuster) q.s. Water for injection q.s.
  • Hydrochloric acid (pH adjuster) q.s. Water for injection q.s.
  • Hydrochloric acid (pH adjuster) q.s. Water for injection q.s.
  • Hydrochloric acid (pH adjuster) q.s. Water for injection q.s.
  • An aqueous solution formulation was prepared in the same manner as in Formulation Example 16 with the exception of using sodium chondroitin sulfate in an amount of 10 mg.
  • An aqueous solution formulation was prepared in the same manner as in Formulation Example 17 with the exception of using sodium chondroitin sulfate in an amount of 10 mg.
  • An aqueous solution formulation was prepared in the same manner as in Formulation Example 18 with the exception of using sodium chondroitin sulfate in an amount of 10 mg.
  • a 5 ml portion of each ophthalmic solution prepared in Formulation Example 1 or 2 was filled into an ophthalmic container (bottle made of colorless polyethylene; nozzle made of colorless polyethylene; cap made of colorless polypropylene, all manufactured by
  • the container, together with an oxygen absorbent (AGELESS) and an oxygen detecting composition (AGELESS EYE) was packaged in a gas barrier film to accomplish secondary packaging, whereby a package according to the present invention was obtained.
  • AGELESS oxygen absorbent
  • AGELESS EYE oxygen detecting composition
  • An oxygen barrier laminated film comprising 15 ⁇ -thick stretched nylon 66 film, 15 ⁇ -thick nylon- ethylene vinyl alcohol copolymer film and 15 ⁇ -thick polyethylene film, the film having an oxygen permeability of 0.8 ml/m 2 -24 hrs at 20 ⁇ C and 65% RH or 1.2 ml/m 2 »24 hrs at 25°C and 65% RH.
  • a vapor/oxygen barrier laminated film comprising 12 ⁇ -thick polyethylene terephthalate film, 12 ⁇ -thick film made of silicon oxide deposited on polyvinyl alcohol, and 50 ⁇ -thick straight-chain low-density polyethylene film, the film having an oxygen permeability of 0.1 ml/m 2 .24 hrs at 20 ⁇ C and 65% RH or 0.1 ml/m 2 .24 hrs at 25°C and 65% RH.
  • the secondary package obtained by packaging the ophthalmic container filled with the ophthalmic solution of Formulation Example 1 using an oxygen barrier laminated film as a gas barrier film is hereinafter referred to as "present product A” .
  • the secondary package obtained by packaging the ophthalmic container filled with the ophthalmic solution of Formulation Example 1 using the vapor/oxygen barrier laminated film as a gas barrier film is hereinafter referred to as "present product B” .
  • the secondary package obtained by packaging the ophthalmic container filled with the ophthalmic solution of Formulation Example 2 using the oxygen barrier laminated film as a gas barrier film is hereinafter referred to as "present product C".
  • the secondary package obtained by packaging the ophthalmic container filled with the ophthalmic solution of Formulation Example 2 using the vapor/oxygen barrier laminate film as a gas barrier film is hereinafter referred to as "present product D".
  • the oxygen concentration in the secondary package was detected by AGELESS EYE.
  • AGELESS EYE is adapted to turn pink in an oxygen concentration of up to 0.1% and adapted to turn blue in an oxygen concentration of not lower than 0.5%. All of "AGELESS EYE" compositions placed in the present products A to D became pink within 3 days.
  • each ophthalmic solution prepared in Formulation Example 1 or 2 was filled into an ophthalmic container (bottle made of colorless polyethylene; nozzle made of colorless polyethylene; cap made of colorless polypropylene, all manufactured by Taisei Kako Co., Ltd.).
  • the container was packaged in an aluminum foil or aluminum-deposited film. Then the space between the ophthalmic container and the secondary package was deaerated by a vacuum packaging machine and nitrogen gas was introduced into the space, whereby present product E (packaged in aluminum foil) and present product F (packaged in an aluminum-deposited film) were obtained.
  • present product G accommodating the aqueous solution formulation of Formulation Example 3
  • present product H accommodating the aqueous solution formulation of Formulation Example 4
  • present product I accommodating the aqueous solution formulation of Formulation Example 5.
  • Preparation Example 4 The aqueous solution formulations prepared in
  • Formulation Examples 6-8 were filled into polyvinyl chloride containers and the containers were packaged, together with an oxygen absorbent (MODULAN) , in a packaging material comprising a laminate of aluminum foil and polyethylene to accomplish secondary packaging, whereby the present product was obtained.
  • MODULAN oxygen absorbent
  • the aqueous solution formulations prepared in Formulation Examples 9-11 were filled into polyester containers and the containers were packaged, together with an oxygen absorbent (SEQUL), in a gas barrier film comprising an ethylene-vinyl alcohol copolymer resin to accomplish secondary packaging, whereby the present product was obtained.
  • SEQUL oxygen absorbent
  • Preparation Example 6 The aqueous solution formulations prepared in Formulation Examples 12-14 were filled into containers of ethylene-vinyl acetate copolymer and secondary packaging was accomplished using a gas barrier film containing polyacrylonitrile. Thereafter carbon dioxide gas was sealed into the deaerated space, whereby the present product was obtained.
  • a 5 ml portion of each ophthalmic solution prepared in Formulation Examples 15, 16 and 17 was filled into an ophthalmic container (bottle made of colorless polyethylene; nozzle made of colorless polyethylene; cap made of colorless polypropylene, all manufactured by Taisei Kako Co., Ltd.).
  • the container, together with an oxygen absorbent ("AGELESS”), was packaged in a packaging material comprising a laminate of aluminum foil and polyethylene to accomplish secondary packaging, whereby the present product was obtained.
  • the secondary package obtained by packaging the ophthalmic container filled with the ophthalmic solution of Formulation Example 15 is hereinafter referred to as "present product J".
  • the secondary package obtained by packaging the ophthalmic container filled with the ophthalmic solution of Formulation Example 16 is hereinafter referred to as "present product K”.
  • the secondary package obtained by packaging the ophthalmic container filled with the ophthalmic solution of Formulation Example 17 is hereinafter referred to as "present product L”.
  • Tables 1 and 2 show the following.
  • the comparative product 1 showed about 10% decrease in the ratio of residual procaterol hydrochloride after 24-week storage at 40°C and 75% RH, whereas the present products A and B showed less than 5% decrease in the ratio of residual procaterol hydrochloride.
  • the comparative product 2 showed about 2% decrease in the ratio of residual procaterol hydrochloride after 12-week storage at 25°C and 75% RH, whereas the present products C and D had no decrease in the ratio of residual procaterol hydrochloride even after 24-week storage.
  • the comparative product 2 decreased by about 6% in the ratio of residual procaterol hydrochloride after 12-week storage at 40°C and 75% RH, whereas the present products C and D decreased by less than 5% in the ratio of residual procaterol hydrochloride even after 24-week storage. It has been be confirmed from these results that the removal of oxygen pronouncedly contributes to stabilization of procaterol hydrochloride.
  • Test Example 2
  • Hartley-strain male guinea pigs were used as model animals. The test was carried out using the animal in a pentobarbital-anesthetized (30 mg/kg, i.p.) state. Test formulations (aqueous solution formulations of Formulation Examples 6-8) were applied by an eyedropper to the animal's right eye and 10 ⁇ l of ophthalmic buffer or physiological salt solution to the animal's left eye. One hour, 2 hours or 3 hours after application, 10 ⁇ l of 2 mg/ml histamine/physiological salt solution was applied to both eyes of the animals to induce conjunctivitis. To the non-treatment group was applied a physiological salt solution in place of histamine. Evans blue was intravenously administered at a dose of 10 mg/ml/kg immediately before application of histamine.
  • Blood was collected from vena cava inferior 30 minutes after application of histamine to determine the absorbance (A g2n ) of blood plasma at 620 nm. Animals' eyelids and conjunctiva were removed. Evans blue was extracted for 2 days using 1.5 ml of acetone-0.5% sodium sulfate (7 : 3, v/v) after which the absorbance of blood plasma at 620 nm was measured. The leakage of blood plasma was calculated by the following equation. Blood plasma leakage ( ⁇ l/tissue)- A620 of tissue extract/A620 of blood plasma X 1500
  • the potency of the drug was expressed in terms of percent control of rise of vascular permeability of the right eye (drug- treated eye) against the left eye (control eye) .
  • the percent control was calculated by the following equation.
  • Test for effect on guinea pigs with histamine- induced conjunctivitis Hartley-strain male guinea pigs were used as model animals. The test was carried out using the animal in a pentobarbital-anesthetized (30 mg/kg, i.p.) state. A test formulation (aqueous solution formulation of Formulation Example 17) was applied by an eyedropper to the animal's right eye and 10 ⁇ l of ophthalmic buffer or physiological salt solution to the animal's left eye. Five minutes or 3 hours after application, 10 ⁇ l of 2 mg/ml histamine/physiological salt solution was applied to both eyes of the animals to induce conjunctivitis.
  • comparative product 5 is one holding said ophthalmic container full of the ophthalmic solution of Formulation Example 15
  • comparative product 6 is one holding said ophthalmic container full of the ophthalmic solution of Formulation Example 16
  • comparative product 7 is one holding said ophthalmic container full of the ophthalmic solution of Formulation Example 17.

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)

Abstract

La présente invention a pour objet de donner une stabilité de stockage à longue échéance à une composition pharmaceutique comportant une solution aqueuse de chlorhydrate de procatérol. Cette invention concerne une solution aqueuse de chlorhydrate de procatérol qui empêche le chlorhydrate de procatérol de se décomposer dans la solution aqueuse du fait de sa réaction d'oxydation.
PCT/JP1996/000772 1995-04-04 1996-03-25 Emballage contenant une formulation de solution aqueuse de chlorhydrate de procaterol et formulation de solution aqueuse de chlorhydrate de procaterol WO1996031195A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP96906940A EP0820274A1 (fr) 1995-04-04 1996-03-25 Emballage contenant une formulation de solution aqueuse de chlorhydrate de procaterol et formulation de solution aqueuse de chlorhydrate de procaterol
MX9707695A MX9707695A (es) 1995-04-04 1996-03-25 Empaque que contiene una formulacion de solucion acuosa de clorhidrato de procaterol, y una formulacion de solucion acuosa de clorhidrato de procaterol.
AU50152/96A AU5015296A (en) 1995-04-04 1996-03-25 Package holding a procaterol hydrochloride aqueous solution formulation, and a procaterol hydrochloride aqueous solution formulation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP7/78564 1995-04-04
JP7856495 1995-04-04

Publications (1)

Publication Number Publication Date
WO1996031195A1 true WO1996031195A1 (fr) 1996-10-10

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Country Status (7)

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EP (1) EP0820274A1 (fr)
KR (1) KR19980703582A (fr)
AR (1) AR002981A1 (fr)
AU (1) AU5015296A (fr)
CA (1) CA2217360A1 (fr)
MX (1) MX9707695A (fr)
WO (1) WO1996031195A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
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WO2002058668A3 (fr) * 2000-12-21 2002-12-27 Alcon Inc Composition de larmes artificielles adaptee pour etre utilisee avec des lentilles de contact
WO2013043832A1 (fr) * 2011-09-22 2013-03-28 Theo Holdings, Llc Solution de dextran hypertonique et procédés de traitement et de prévention de l'érosion cornéenne récidivante
WO2017082771A1 (fr) * 2015-11-10 2017-05-18 Общество с ограниченной ответственностью "ДИАМЕД-фарма" Préparation pharmaceutique
RU2688935C2 (ru) * 2014-05-07 2019-05-23 Крома-Фарма Гезелльшафт М.Б.Х. Водный офтальмологический раствор и способ лечения синдрома сухих глаз
CN114159398A (zh) * 2021-03-22 2022-03-11 南京艾德加生物制药科技有限公司 一种盐酸丙卡特罗口服固体组合物及其制备方法

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EP3342398A4 (fr) * 2015-10-06 2019-03-20 G-Treebnt Co., Ltd. Procédé de préparation de préparation ophtalmique contenant de la thymosine bêta-4
RU2612019C1 (ru) * 2015-12-11 2017-03-01 Общество с ограниченной ответственностью "ДИАМЕД-фарма" Способ производства инъекционной формы препарата на основе хондроитина сульфата

Citations (2)

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Publication number Priority date Publication date Assignee Title
EP0443027A1 (fr) * 1988-11-11 1991-08-28 Kurita Water Industries Ltd. Medicament
EP0609042A1 (fr) * 1993-01-25 1994-08-03 Seikagaku Kogyo Kabushiki Kaisha (Seikagaku Corporation) Composition pharmaceutique et procédé pour sa préparation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0443027A1 (fr) * 1988-11-11 1991-08-28 Kurita Water Industries Ltd. Medicament
EP0609042A1 (fr) * 1993-01-25 1994-08-03 Seikagaku Kogyo Kabushiki Kaisha (Seikagaku Corporation) Composition pharmaceutique et procédé pour sa préparation

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002058668A3 (fr) * 2000-12-21 2002-12-27 Alcon Inc Composition de larmes artificielles adaptee pour etre utilisee avec des lentilles de contact
WO2013043832A1 (fr) * 2011-09-22 2013-03-28 Theo Holdings, Llc Solution de dextran hypertonique et procédés de traitement et de prévention de l'érosion cornéenne récidivante
US9351990B2 (en) 2011-09-22 2016-05-31 Theo Holdings, Llc Hypertonic dextran solution and methods of treating and preventing recurrent corneal erosion
US9351991B2 (en) 2011-09-22 2016-05-31 Theo Holdings, Llc Hypertonic dextran solution and methods of treating and preventing recurrent corneal erosion
US9636355B2 (en) 2011-09-22 2017-05-02 Theo Holdings, Llc Hypertonic dextran solution and methods of treating and preventing recurrent corneal erosion
RU2688935C2 (ru) * 2014-05-07 2019-05-23 Крома-Фарма Гезелльшафт М.Б.Х. Водный офтальмологический раствор и способ лечения синдрома сухих глаз
WO2017082771A1 (fr) * 2015-11-10 2017-05-18 Общество с ограниченной ответственностью "ДИАМЕД-фарма" Préparation pharmaceutique
CN114159398A (zh) * 2021-03-22 2022-03-11 南京艾德加生物制药科技有限公司 一种盐酸丙卡特罗口服固体组合物及其制备方法
CN114159398B (zh) * 2021-03-22 2023-05-23 南京艾德加生物制药科技有限公司 一种盐酸丙卡特罗口服固体组合物及其制备方法

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AU5015296A (en) 1996-10-23
AR002981A1 (es) 1998-05-27
EP0820274A1 (fr) 1998-01-28
CA2217360A1 (fr) 1996-10-10
MX9707695A (es) 1997-12-31
KR19980703582A (ko) 1998-11-05

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